Verteporfin fluorescence in antineoplastic-treated pancreatic cancer cells found concentrated in mitochondria.

BACKGROUND: Traditional treatments for pancreatic cancer (PC) are inadequate. Photodynamic therapy (PDT) is non-invasive, and proven safe to kill cancer cells, including PC. However, the mitochondrial concentration of the photosensitizer, such as verteporfin, is key. AIM: To investigate the distribution of fluorescence of verteporfin in PC cells treated with antitumor drugs, post-PDT. METHODS: Workable survival rates of PC cells (AsPC-1, BxPC-3) were determined with chemotherapy [doxorubicin (DOX) and gemcitabine (GEM)] and non-chemotherapy [sirolimus (SRL) and cetuximab (CTX)] drugs in vitro, with or without verteporfin, as measured via MTT, flow cytometry, and laser confocal microscopy. Reduced cell proliferation was associated with GEM that was more enduring compared with DOX. Confocal laser microscopy allowed observation of GEM- and verteporfin-treated PC cells co-stained with 4',6-diamidino-2-phenylindole and MitoTracker Green to differentiate living and dead cells and subcellular localization of verteporfin, respectively. RESULTS: Cell survival significantly dropped upon exposure to either chemotherapy drug, but not to SRL or CTX. Both cell lines responded similarly to GEM. The intensity of fluorescence was associated with the concentration of verteporfin. Additional experiments using GEM showed that survival rates of the PC cells treated with 10 µmol/L verteporfin (but not less) were significantly lower relative to nil verteporfin. Living and dead stained cells treated with GEM were distinguishable. After GEM treatment, verteporfin was observed primarily in the mitochondria. CONCLUSION: Verteporfin was observed in living cells. In GEM -treated human PC cells, verteporfin was particularly prevalent in the mitochondria. This study supports further study of PDT for the treatment of PC after neoadjuvant chemotherapy.

Generalization analysis of deep CNNs under maximum correntropy criterion.

Convolutional neural networks (CNNs) have gained immense popularity in recent years, finding their utility in diverse fields such as image recognition, natural language processing, and bio-informatics. Despite the remarkable progress made in deep learning theory, most studies on CNNs, especially in regression tasks, tend to heavily rely on the least squares loss function. However, there are situations where such learning algorithms may not suffice, particularly in the presence of heavy-tailed noises or outliers. This predicament emphasizes the necessity of exploring alternative loss functions that can handle such scenarios more effectively, thereby unleashing the true potential of CNNs. In this paper, we investigate the generalization error of deep CNNs with the rectified linear unit (ReLU) activation function for robust regression problems within an information-theoretic learning framework. Our study demonstrates that when the regression function exhibits an additive ridge structure and the noise possesses a finite pth moment, the empirical risk minimization scheme, generated by the maximum correntropy criterion and deep CNNs, achieves fast convergence rates. Notably, these rates align with the mini-max optimal convergence rates attained by fully connected neural network model with the Huber loss function up to a logarithmic factor. Additionally, we further establish the convergence rates of deep CNNs under the maximum correntropy criterion when the regression function resides in a Sobolev space on the sphere.

[Effect and mechanism of gastrodin in relaxing isolated thoracic aorta rings in rats].

OBJECTIVE: To investigate the effect of gastrodin in relaxing isolated thoracic aorta rings in rats and discuss its possible mechanism. METHOD: Isotonic tension of isolated thoracic aortic rings in rats with norepineprine (NE) and KCl was recorded to observe the vasodilatory effect of gastrodin and the influence of various drugs on it. RESULT: Gastrodin had the effect in relaxing thoracic aortas with or without endothelium, and there was no significant difference. NG-nitro-L-argininemethylester (L-NAME, 1 x 10(-4) mol x L(-1)), methylene blue (MB, 1 x 10(-5) mol x L(-1)), indomethacin (INDO, 1 x 10(-5) mol x L(-1)) had no effect on the vasodilation action of gastrodin on thoracic aortas precontracted by NE. 4-aminopyrimide (4-AP, 1 x 10(-4) mol x L(-1)), tetrathylamonium (TEA, 1 x 10(-3) mol x L(-1)), BaCl2 (1 x 10(-4) mol x L(-1)) and glibenclamide (Gli, 1 x 10(-5) mol x L(-1)) could inhibit gastrodin's effect in relaxing thoracic aorta rings. In the absence of Ca2+, pre-incubated gastrodin showed a notable inhibitory effect in relaxing NE contraction. CONCLUSION: Gastrodin shows a dose-dependent and endothelium-independent effect in relaxing rat isolated thoracic aorta rings. The mechanism is related to K+ channel, inhibition of release of Ca+ stored in endoplasmic reticulum of vascular smooth muscle cells and inflow of external calcium Ca2+.